A Prospective clinical trial of hormone therapy in postmenopausal bone loss. Fracture incidence is a major health care problem in this country which occurs as a complication of postmenopausal and age-related bone loss. Costs exceed one billion dollars annually, and mortality (10%) and morbidity from fractures are both considerable. Previous reports have shown the efficacy of long term high dose estrogen on the inhibition of postmenopausal bone loss, and two recent reports have demonstrated a reduced fracture incidence in women treated with estrogen. But concern has been raised over the reported increase in endometrial cancer in patients given the same doses of estrogen that are used to inhibit bone loss. There are two main objectives in this project. First, to study the efficacy of low dose hormone regimens using either estrogen, progestogen, or a combination of the two to inhibit postmenopausal bone loss. Secondly, to study the long term safety of these hormone preparations, particularly with regard to their effect on the uterus. The project consists of a three-year study involving eighty postmenopausal women who are in good health. They will be entered into a double blind randomized trial in four equal groups. Three different hormone preparations and a placebo will be compared for their effect on bone loss in the postmenopausal period. The drugs used will be as follows: low dose estrogen (Premarin, 0.3 mg/day), low dose progestogen (Provera, 20 mg/day), a combination of estrogen and progestogen together (doses as above) and a placebo. The efficacy of the hormones will be evaluated by using photon absorptiometry of the radius and dual photon absorptiometry of the spine to detect changes in bone density. Changes in cortical bone will be evaluated by radiogrammetry of the metacarpal. The safety of the estrogen and progestogen therapies will be assessed by histological examination of endometrial biopsy. The long term objectives of this project are to demonstrate the safety of low dose hormone preparations which are able to prevent bone loss and in the long term reduce fracture incidence without causing significant endometrial stimulation.